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Sphingomyelin synthases regulate protein trafficking and secretion.

Marimuthu Subathra1, Asfia Qureshi, Chiara Luberto

  • 1Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, South Carolina, United States of America.

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Sphingomyelin synthases (SMS1 and 2) regulate protein trafficking and secretion. Inhibiting these enzymes disrupts the trans-Golgi network, impacting cellular processes like insulin secretion.

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Published on: March 14, 2021

Area of Science:

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Background:

  • Sphingomyelin synthases (SMS1 and 2) produce sphingomyelin and diacylglycerol (DAG).
  • SMS1 is Golgi-localized, while SMS2 is found at the Golgi and plasma membrane.
  • Previous work linked SMS activity to DAG formation and protein kinase D (PKD) localization at the Golgi.

Purpose of the Study:

  • To investigate the role of SMS1 and SMS2 in trans-Golgi network (TGN) mediated protein trafficking and secretion.
  • To determine if SMS enzymes influence TGN membrane dynamics.
  • To assess the impact of SMS inhibition on insulin secretion in beta cells.

Main Methods:

  • Down-regulation of SMS1 and/or SMS2 using genetic or chemical inhibitors.
  • Tracking the trafficking of vesicular stomatitis virus G protein tagged with GFP (VSVG-GFP) from the TGN to the cell surface.
  • Microscopic analysis of TGN morphology, including membrane fission.
  • Measuring insulin secretion in rat INS-1 cells following SMS inhibition.

Main Results:

  • Down-regulation of SMS1 or SMS2 significantly slowed the transport of VSVG-GFP from the TGN to the cell surface.
  • Inhibition of SMS enzymes led to tubular protrusions from the TGN, suggesting impaired membrane fission.
  • SMS inhibition markedly reduced insulin secretion in rat INS-1 cells.
  • PKD localization to the Golgi was reduced upon SMS down-regulation.

Conclusions:

  • SMS1 and SMS2 are key regulators of TGN-mediated protein trafficking and secretion.
  • SMS enzymes influence TGN membrane dynamics, potentially through PKD signaling.
  • These findings highlight the role of sphingomyelin metabolism in cellular secretion processes, including insulin release.